[Show abstract][Hide abstract] ABSTRACT: Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections.
[Show abstract][Hide abstract] ABSTRACT: Siderophores are important for the growth of bacteria or the applications in treatment of iron overload-associated diseases due to the iron-chelating property. Salicylate synthase played a key role in the biosynthesis of some NRPS-derived siderophores by the providing of an iron coordination moiety as the initial building block. A new salicylate synthase, namely AmS, was identified in the biosynthesis pathway of siderophore amychelin in Amycolatopsis methanolica 239T, since it shunt chorismate, an integrant precursor, from primary to secondary metabolite flow. The amino acid sequence alignment and phylogenetic analysis showed that AmS grouped into a new cluster. In vitro assays of AmS revealed its wide temperature tolerance ranged from 0 to 40 °C and narrow pH tolerant ranged from 7.0 to 9.0. AmS was resistant to organic solvents and non-ionic detergents. Moreover, AmS converted chorismate to salicylate with K
of 129.05 μM, k
cat of 2.20 min−1 at optimal conditions, indicating its low substrate specificity and comparable velocity to reported counterparts (Irp9 and MbtI). These properties of AmS may improve the iron-seizing ability of A. methanolica to compete with its neighbors growing in natural environments. Most importantly, serine and cysteine residues were found to be important for the catalytic activity of AmS. This study presented AmS as a new cluster of salicylate synthase and the reaction mechanism and potential applications of salicylate synthase were highlighted as well.
[Show abstract][Hide abstract] ABSTRACT: A Gram-stain positive, aerobic, non-motile actinobacterium, designated DSXY973T was isolated from soil samples collected from Xinjiang desert using medium supplemented with resuscitation promoting factor (Rpf), and subjected to polyphasic taxonomic investigation. Phylogenetic analysis based on 16S rRNA gene sequences revealed that DSXY973T was belonged to the genus Arthrobacter and most close to Arthrobacter oryzae JCM 15922T with 97.1% similarity. The DNA G+C content was 67.6%. Cells of strain DSXY973T mainly contained MK-9(H2), and cell wall contained L-lysine as primary diamino acid. The major cellular fatty acids were anteiso-C15:0, anteiso-C17:0 and iso-C15:0. Strain DSXY973T was positive for catalase activity and negative for oxidase activity. On the basis of phylogenetic position and phenotypic properties, strain DSXY973T represents a novel species of the genus Arthrobacter, for which the name Arthrobacter liuii sp. nov. is proposed. The type strain is DSXY973T (= CGMCC1.12778T = JCM 19864T).
International Journal of Systematic and Evolutionary Microbiology 12/2014; 65(Pt 3). DOI:10.1099/ijs.0.000037 · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A Gram-positive, spore-forming, rod-shaped actinomycete, designated XJ46(T) was isolated from Xinjiang Uyghur Autonomous Region, China and subjected to a polyphasic taxonomic analysis. Morphological and chemotaxonomic characteristics of strain XJ46(T) were identified as a member of the genus Prauserella. The phylogenetic tree based on 16S rRNA gene sequences showed that XJ46(T) had the highest similarity (95.9%) with Prauserella marina MS498(T). Based on its phenotypic characteristics, chemotaxonomic analysis and 16S rRNA gene sequence analysis, strain XJ46(T) was proposed to represent a novel species of the genus Prauserella, named Prauserella shujinwangii sp. nov. The type strain is XJ46(T) (= CGMCC 4.7125(T) = JCM 19736(T)).
[Show abstract][Hide abstract] ABSTRACT: During the systematic screening of active compounds from marine-derived fungi, the extract of a strain of Aspergillus versicolor MF359 isolated from a marine sponge of Hymeniacidon perleve was identified for detailed chemical investigation. Three new secondary metabolites, named hemiacetal sterigmatocystin (1), acyl-hemiacetal sterigmatocystin (2), and 5-methoxydihydrosterigmatocystin (3), together with a known compound, aversin (4), were characterized. 1 represents a first structure of sterigmatocystin hemiacetal from nature. The antibacterial activities of these identified compounds were evaluated against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Compound 3 showed activity against S. aureus and B. subtilis with MIC values of 12.5 and 3.125 μg/mL, respectively.
[Show abstract][Hide abstract] ABSTRACT: Finding effective drugs to treat fungal infections has important clinical significance based on high mortality rates, especially in an immunodeficient population. Traditional antifungal drugs with single targets have been reported to cause serious side effects and drug resistance. Nowadays, however, drug combinations, particularly with respect to synergistic interaction, have attracted the attention of researchers. In fact, synergistic drug combinations could simultaneously affect multiple subpopulations, targets, and diseases. Therefore, a strategy that employs synergistic antifungal drug combinations could eliminate the limitations noted above and offer the opportunity to explore this emerging bioactive chemical space. However, it is first necessary to build a powerful database in order to facilitate the analysis of drug combinations. To address this gap in our knowledge, we have built the first Antifungal Synergistic Drug Combination Database (ASDCD), including previously published synergistic antifungal drug combinations, chemical structures, targets, target-related signaling pathways, indications, and other pertinent data. Its current version includes 210 antifungal synergistic drug combinations and 1225 drug-target interactions, involving 105 individual drugs from more than 12,000 references. ASDCD is freely available at http://ASDCD.amss.ac.cn.
PLoS ONE 01/2014; 9(1):e86499. DOI:10.1371/journal.pone.0086499 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most screening approaches produce compounds that target survival genes and are likely to generate resistance over time. Simply having more drugs does not address the potential emergence of resistance caused by target mutation, drug efflux pumps over-expression, and so on. There is a great need to explore new strategies to treat fungal infections caused by drug-resistant pathogens. In this study, we found that azole-resistant Candida albicans with CaCDR1 and CaCDR2 over-expression is hypersensitive against amphotericin B (AmB) by our high throughput synergy screening (HTSS). In contrast, Δcdr1 and Δcdr2 knockout strains were resistant to AmB. Moreover, clinical isolates with increased expression of CaCDR1 and CaCDR2 demonstrated susceptibility to AmB, which can also synergize with the efflux pumps inducer fluphenazine (FPZ). Finally, the increased drug susceptibility to AmB in azole-resistant C. albicans with drug efflux pumps over-expression was consistent with the elevated expression of CaERG11 and its associated ergosterols in clinical isolates. Our data implies that the level of ergosterol contents determines the susceptibility to azoles and AmB in C. albicans. Deep understanding of the above mechanisms would offer new hope to treat drug-resistant C. albicans.
[Show abstract][Hide abstract] ABSTRACT: The exponential growth of gigantic biological data from various sources, such as protein-protein interaction (PPI), genome sequences scaffolding, Mass spectrometry (MS) molecular networking and metabolic flux, demands an efficient way for better visualization and interpretation beyond the conventional, two-dimensional visualization tools.
We developed a 3D Cytoscape Client/Server (3DScapeCS) plugin, which adopted Cytoscape in interpreting different types of data, and UbiGraph for three-dimensional visualization. The extra dimension is useful in accommodating, visualizing, and distinguishing large-scale networks with multiple crossed connections in five case studies.
Evaluation on several experimental data using 3DScapeCS and its special features, including multilevel graph layout, time-course data animation, and parallel visualization has proven its usefulness in visualizing complex data and help to make insightful conclusions.
[Show abstract][Hide abstract] ABSTRACT: As part of a search for antitubercular substances from natural sources, we screened a library of endophytic microbes (50 strains and 300 crude extracts in total) isolated from traditional Chinese medicines (TCMs) for growth inhibitory activity against Bacillus Calmette-Guérin (BCG). The crude extract of Streptomyces sp. strain Y3111, which was associated with the stems of Heracleum souliei, showed good anti-BCG activity with an MIC value of 12.5 μg/mL. Bioassay-guided isolation led to four new pluramycin-type compounds, heraclemycins A-D (1-4). Their structures were determined by different spectroscopic techniques including HRMSESI, 1D NMR, and 2D NMR. This is the first report of pluramycin analogues produced by TCM endophytic microbes as well as the first example of BCG-selective pluramycins. Heraclemycin C (3) showed selective antitubercular activity against BCG with a MIC value of 6.25 μg/mL and a potential new mode of action.
[Show abstract][Hide abstract] ABSTRACT: Chemical analysis of an East China Sea marine-derived fungus, Aspergillus sydowii (MF357) returned three new tris-pyrogallol ethers, sydowiols A-C (1-3), and two known bis-pyrogallol ethers, violaceols I (4) and 11 (5). Structures were assigned on the basis of detailed spectroscopic analysis and by consideration of symmetry. Sydowiols A (1) and C (3) were responsible for the inhibitory activity detected in the crude fungal extract against Mycobacterium tuberculosis protein tyrosine phosphatase A (PtpA).
[Show abstract][Hide abstract] ABSTRACT: A high-throughput screening of a microbial natural product library led to the discovery of two novel compounds named nivetetracyclates A and B (1 and 2), which were produced by Streptomyces niveus designated as LS2151. The backbone of the compounds contains a hydrotetracyclate not previously reported from a natural source. The structures of the compounds were elucidated by spectroscopic methods. The nivetetracyclates exhibited activity against human HeLa cells.
[Show abstract][Hide abstract] ABSTRACT: A Gram-positive, endospore-forming, rod-shaped bacterium, designated isolate J2(T) was isolated from a soil sample from Xinjiang Uyghur Autonomous Region, China. The isolate was observed to grow at 16-46 °C and pH 6.5-8.0. Chemotaxonomic analysis showed menaquinone-7 (MK-7) to be the major isoprenoid quinone; diphosphatidylglycerol, phosphatidylglycerol, one aminophospholipid, two phosphoglycolipids and one glycolipid as the major cellular polar lipids; and anteiso-C15:0, iso-C15:0, anteiso-C17:0 and C16:0 as the major fatty acids. Comparative analyses of the 16S rRNA gene sequence showed that strain J2(T) is most closely related to Gracilibacillus ureilyticus (with 98.8 % similarity), Gracilibacillus dipsosauri (97.2 %), Gracilibacillus quinghaiensis (97.1 %) and Gracilibacillus thailandensis (97.0 %). The DNA-DNA reassociation values between strain J2(T) and G. ureilyticus MF38(T), G. dipsosauri DD1(T), G. quinghaiensis YIM-C229(T) and G. thailandensis TP2-8(T) were 29.8 ± 3.7, 23.0 ± 3.5, 15.8 ± 4.9 and 15.9 ± 5.0 %, respectively. The genomic DNA G+C content of strain J2(T) was determined to be 36.5 mol%. Based on these data, strain J2(T) is considered as a novel species of the genus Gracilibacillus, for which the name Gracilibacillus xinjiangensis sp. nov. is proposed. The type species is J2(T) (= CGMCC 1.12449(T) = JCM 18859(T)).
Antonie van Leeuwenhoek 08/2013; 104(5). DOI:10.1007/s10482-013-9992-3 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the course of a screening program for bioactive compounds from a marine natural product library, a newly isolated Actinomycetes strain, designated as MS100061, exhibited strong anti-Mycobacterium bovis Bacillus Calmette-Guérin (BCG) activity. The strain belongs to the genus Streptomyces according to its morphological and 16S rDNA phylogenetic analysis. Bioassay-guided isolation resulted in a new spirotetronate, lobophorin G (1), together with two known compounds, lobophorins A (2) and B (3). The structures were elucidated by extensive spectroscopic methods and comparison with literatures. Compounds 1-3 were subjected to anti-BCG, antituberculosis, and antibacterial screening and exhibited potent anti-BCG activity with minimum inhibitory concentration (MIC) values of 1.56, 1.56, and 0.78 μg/ml, respectively, and moderate anti-Mycobacterium tuberculosis H37Rv activity with MIC values of 32, 32, and 16 μg/ml, respectively. The MIC values of compounds 1-3 against Bacillus subtilis were 3.125, 12.5, and 1.56 μg/ml, respectively, indicating great potential for antibacterial drugs. In addition, this is the first report of the anti-BCG and antituberculosis activities of lobophorins.
[Show abstract][Hide abstract] ABSTRACT: Three new mixed terpenoids, tricycloalternarenes (TCAs) F-H (1-3), together with ten known tricycloalternarenes (4-13), were isolated from the Czapek's culture of an endophytic fungus Ulocladium sp. Their structures were identified by extensive spectroscopic experiments (NMR and MS) and comparison with literature data. TCA 1b (5) showed weak activity against the Bacille Calmette-Guerin strain with the MIC of 125 μg/ml. TCA 9b (10) exhibited strong cytotoxic activity against Hela cell line with IC(50) of 8.58 μM.
[Show abstract][Hide abstract] ABSTRACT: A Gram-positive, endospore-forming, rod-shaped bacterium, designated isolate J4(T), was isolated from a neutral saline lake sample from Xinjiang Uyghur Autonomous Region, China, and subjected to a polyphasic taxonomic investigation. Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain J4(T) is most closely related to Salinibacillus aidingensis 25-7(T) (with 96.7 % similarity), Salinibacillus kushneri 8-2(T) (96.5 %), Ornithinibacillus scapharcae TW25(T) (96.4 %), Salirhabdus euzebyi CVS-14(T) (96.4 %) and Ornithinibacillus californiensis MB-9(T) (96.2 %). Chemotaxonomic analysis showed menaquinone-7 (MK-7) to be the major isoprenoid quinone of strain J4(T); diphosphatidylglycerol and phosphatidylglycerol were the major cellular polar lipids and the cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid. The major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The genomic DNA G+C content of strain J4(T) was determined to be 36.2 mol%. Strain J4(T) was positive for catalase activity and negative for oxidase activity. Strain J4(T) was observed to grow at 25-50 °C (optimal 35-42 °C), pH 6.5-8.0 (optimal 7.0-7.5) and in media containing 1-21 % (w/v) NaCl (optimal 9-12 %). Based on these data, strain J4(T) represents a novel species of the genus Salinibacillus and the name Salinibacillus xinjiangensis sp. nov. is proposed. The type strain is J4(T) ( = CGMCC 1.12331(T) = JCM 18732(T)).
International Journal of Systematic and Evolutionary Microbiology 01/2013; 64(Pt 1):27-32. DOI:10.1099/ijs.0.053306-0 · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A total of 29 novel sulfenamide compounds were synthesized, spectroscopically characterized and evaluated in vitro for antimicrobial activity against various infectious pathogens. Compounds 1b and 2c exhibited potent inhibition against clinical Methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentration (MIC) values of 1.56μg/mL.
[Show abstract][Hide abstract] ABSTRACT: An Aspergillus versicolor isolated from sediment collected from the Bohai Sea, China, yielded the new dimeric diketopiperazine brevianamide S (1), together with three new monomeric cometabolites, brevianamides T (2), U (3), and V (4). Structures were determined by detailed spectroscopic analysis. Brevianamide S exhibited selective antibacterial activity against Bacille Calmette-Guérin (BCG), suggestive of a new mechanism of action that could inform the development of next-generation antitubercular drugs.
[Show abstract][Hide abstract] ABSTRACT: There is growing interest in discovery of novel bioactive natural products from Burkholderia thailandensis. Here we report a significantly improved genome sequence and reannotation of Burkholderia thailandensis MSMB43, which will facilitate the discovery of new natural products through genome mining and studies of the metabolic versatility
of this bacterium.
Journal of bacteriology 09/2012; 194(17):4749-50. DOI:10.1128/JB.00931-12 · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A Gram-positive, spore-forming, rod-shaped bacterium, designated J1T was isolated from deep sea mud collected from the South China Sea, and subjected to polyphasic taxonomic investigation. Phylogenetic analysis based on 16S rRNA gene sequences revealed that J1T clustered with the type strains of Amphibacillus cookii, Amphibacillus sediminis and Amphibacillus jilinensis, and exhibited the range of similarity of 93.9%-97.0% to the species in genus Amphibacillus. The DNA G+C content was 36.7%. Chemotaxonomic analysis showed no quinones, and the cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid for strain J1T. The major cellular fatty acids were iso-C15:0 and anteiso-C15:0. The strain J1T was positive for catalase activity and negative for oxidase activity. On the basis of phylogenetic position and phenotypic properties, strain J1T represents a new species of the genus Amphibacillus and the name Amphibacillus marinus sp. nov. is proposed. The type strain is J1T (=CGMCC 1.10434T = JCM 17099T).
International Journal of Systematic and Evolutionary Microbiology 08/2012; 63(Pt 4). DOI:10.1099/ijs.0.045807-0 · 2.51 Impact Factor